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BIOL 432 Final > Calcium Regulation > Flashcards

Calcium Regulation Flashcards

1
Q

What are the three sites of extracellular fluid interface for calcium exchange?

A
  1. the intestine
  2. the bone
  3. the renal tubule (kidney)
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2
Q

What regulates calcium exchange?

A
  1. vitamin D
  2. parathyroid hormone
  3. calcitonin
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3
Q

How much of the body’s total level of calcium is in the extracellular fluid?

A
  • only 1% because mostly in bone
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4
Q

What calcium is regulatory?

A
  • Ca2+ is regulatory, whereas bound calcium is not
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5
Q

Why is calcium so important?

A
  • proper function of many tissues requires appropriate extracellular and/or intracellular calcium
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6
Q

What functions require appropriate levels of extracellular calcium?

A
  1. excitation/contraction of heart and muscles
  2. synapse and other nervous system functions
  3. platelet aggregation, coagulation
  4. secretion of hormones and other regulators by exocytosis
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7
Q

What regulates intracellular calcium and how much less is intracellular calcium then extracellular?

A
  • ATP-dependent calcium pumps and Na+/Ca2+ exchanger

- 10,000 fold less than outside cell

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8
Q

How is calcium let into the cell?

A
  • rapid flow through calcium channels (receptor or voltage controlled)
  • release from internal stores from ER or mitochondria (IP3 signaling)
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9
Q

What happens if you remove the parathyroid gland where parathyroid hormone is made?

A
  • severe hypocalcemia, tetany and death
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10
Q

Where are thyroid C cells made?

A
  • in the parafollicular cells
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11
Q

What happens if you remove the parafollicular cells?

A
  • no calcitonin made

- no real disease

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12
Q

What happens if you have a tumor in the parathyroid gland?

A
  • excess calcitonin

- no real disease

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13
Q

What can we use calcitonin to treat?

A
  • lytic Paget’s disease, hypercalcemia, and osteoporosis
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14
Q

Where are there vitamin D receptors?

A
  • bone, kidney, intestine, but also others like immune cells, testis, and breast
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15
Q

Why does vitamin D have important implications for cancer?

A
  • cells respond to vitamin D with antiproliferation
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16
Q

What functions is vitamin D good for?

A
  • hormone synthesis and secretion

- regulates genes via a nuclear receptor

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17
Q

What is an osteoblast?

A

bone forming cell

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18
Q

What receptors does an osteoblast have?

A
  • receptors for parathyroid hormone and vitamin D
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19
Q

What does an osteoblast stimulate?

A
  • stimulates an osteoclast
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20
Q

What is an osteoclast?

A
  • bone resorption cell
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21
Q

What receptors does an osteoclast have?

A
  • receptor for calcitonin which inhibits it
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22
Q

What does an osteoclast do?

A
  • moves to bone surface and secretes acid and enzymes

- does not divide

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23
Q

What are the steps in the bone cycle?

A 
A) resting on bone surface
B) osteoclasts dig a hole
C) phagocytes mop up 
D) osteoblasts are recruited
E) osteoblast secrete bone matrix
F-G) calcification and mineralization
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24
Q

What materials are fixed in one crystals?

A
  • calcium and phosphate
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25
Q

How long does the bone cycle take?

A

~ 6 months

- if not balanced will lose bone

26
Q

Where is calcitonin made?

A
  • parafollicular cells in thyroid gland (C cells)
27
Q

Where is parathyroid hormone made?

A
  • in parathyroid cells of parathyroid gland
28
Q

Where is vitamin D made?

A
  • in combination of skin, liver and kidney
29
Q

What type of hormone is parathyroid hormone?

A
  • a peptide hormone
30
Q

How does parathyroid hormone affect kidney calcium?

A
  • uses a GPCR that signals Ca2+ channels to open and uptake from urinary tract and increase plasma Ca2+
31
Q

How does parathyroid hormone affect bone calcium?

A
  • stimulates osteoclasts (indirect) causing bone resorption (bone releases Ca2+)
32
Q

How does parathyroid hormone affect intestine calcium?

A
  • increases absorption of calcium indirectly via up regulation of active vitamin D
33
Q

What happens to parathyroid synthesis in response to calcium levels?

A

inhibition of synthesis and secretion

34
Q

What is the calcium concentration in parathyroid cells controlled by?

A
  • extracellular calcium ion sensor receptor (CaR)
35
Q

What does intracellular magnesium result in?

A

secretion signal after stimulus

36
Q

What are the effects of cacitonin on the body?

A
  • inhibits Ca2+ reaborption in kidney
  • promotes deposition of Ca2+ into bones (inhibits osteoclasts, stimulatse osteoblasts)
  • inhibits Ca2+ absorption by the intestines
  • lowers Ca2+ levels in blood
37
Q

What type of hormone is calcitonin?

A
  • peptide hormone
38
Q

What receptors does calcitonin bind?

A
  • GPCR on osteoclasts and kidney tubules with G alpha s
39
Q

What is the main effect of calcitonin?

A
  • inhibits osteoclasts so lowers blood Ca2+
40
Q

Where is calcitonin secreted from?

A
  • parafollicular cells (thyroid C cells)
41
Q

What is calcitonin secretion regulated by?

A
  • regulated by CaR found on parathyroid gland

- Ca2+ leads to secretion

42
Q

What is vitamin D essential for the formation of and why?

A

normal bones and teeth by maintaining normal blood levels of calcium and phosphorus
- many important effects including cell differentiation and development

43
Q

What are some of the other names for vitamin D?

A
  • several fat-soluble vitamins (D1, D2, D3)

- calcitriol (active vitamin D)

44
Q

Why is vitamin D referred to as a hormone?

A
  • we make most of it (~90%)
  • levels are regulated
  • uses nuclear receptor to affect transcription
45
Q

How much sun exposure do we need?

A
  • 10-15 minutes of sun exposure of reasonable intensity at least two times per week
46
Q

Where is vitamin D stored in the body to use during the winter?

A
  • stored in the liver and fat
47
Q

Why can’t we make vitamin D indoors?

A
  • we need ~295 nm UVB
48
Q

Why are tanning beds an ineffective way t get vitamin D?

A
  • causes skin cancer, eye damage, and premature aging
49
Q

What type of receptor does vitamin D use?

A
  • same type of high affinity nuclear receptor to affect transcription as steroids
50
Q

Where are vitamin D receptors located?

A
  • bone, kidney, gut, immune cells, testis, breast
51
Q

What is vitamin D upregulated by?

A
  • low phosphorous, low calcium, high parathyroid hormone and low vitamin D
52
Q

How is vitamin D regulated when concentration is high?

A
  • feedback inhibits own receptor transcription

- upregulates hydroxylase (which breaks down vitamin D)

53
Q

What is the general action of vitamin D?

A

1) vitamin D receptor froms heterodimer with retinoic X receptor on vitamin D response element on the DNA
2) affects transcription and production of proteins for cell differentiation and development and maintains normal blood levels of calcium and phosphorus

54
Q

What are some specific actions of vitamin D?

A

1) increase calcium channels and calcium-binding protein in intestine and brings calcium into cell
2) increase osteocalcin in bone cells
3) decrease parathyroid hormone synthesis

55
Q

Where is vitamin D first transported to and what happens there?

A
  • D3 and D2 transported to liver where cytochrome P450 oxidase enzyme acts on it
56
Q

From the liver, where is vitamin D transported and what happens there?

A
  • transported to kidney where another cytochrome P450 oxidase enzyme converts
  • rate limiting step
57
Q

What are the conditions in the kidney where vitamin D is mainly controlled?

A
  • low phosphorous
  • low calcium
  • high parathyroid hormone favor calcitriol
  • cytochrome P450 enzyme oxidizes vitamin D precursor
58
Q

Where is vitamin D deactivated and cleared out?

A
  • in the liver, hydroxylase deactivates it

- kidneys clear body of it

59
Q

How does vitamin D promote calcium ion uptake in the intestine?

A

1) calcitriol diffuses across the membrane
2) binds vitamin D receptor in nucleus (with RXR)
3) upregulates mRNA for genes like calcium channels, calcium-binding protein and vitamin D receptor
4) Calcium ion transported from lumen across calcium channel, binds calcium binding protein and transported and moved across intestinal cells
5) calcium ion released into blood or fluid and saved from excretion path

60
Q

How does vitamin D affect bone formation/resorption?

A

1) increase transcription of calcium channels, calcium-binding protein, vitamin D receptor and osteocalcin (bone formation protein)
2) decrease parathyroid hormone
3) differentiation of hemapoetic, epidermal, hair follicle, osteoblast and osteoclast cells

BIOL 432 Final (14 decks)

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